| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 3. |
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| 4. |
- Brunner, Fabian J., et al.
(författare)
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10215, s. 2173-2183
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
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| 5. |
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| 6. |
- Axelsson, Annika, et al.
(författare)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 7. |
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| 8. |
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| 9. |
- Eliasson, L, et al.
(författare)
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Observations of electron conics by the Viking satellite
- 1996
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. - 0148-0227. ; 101:A6, s. 13225-13238
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Electron angular distributions peaked at oblique angles to the magnetic field, electron conics, are frequently found in the Viking data at all magnetic local times, but with a maximum in the dusk sector. Several types of electron conics have been observed
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| 10. |
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| 11. |
- Gromov, Sergey P, et al.
(författare)
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Synthesis, Structure, Spectroscopic Studies, and Complexation of Novel Crown Ether Butadienyl Dyes
- 2002
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Ingår i: Helvetica Chimica Acta. ; 85:1, s. 60-81
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Tidskriftsartikel (refereegranskat)abstract
- Butadienyl dyes of the benzothiazole series with various fragments of benzocrown ethers 1a-c were synthesized for the first time. The structures and spectral properties of crown-containing butadienyl dyes and their complexes with alkali and alkaline-earth metal cations were studied by X-ray diffraction analysis and 1H-NMR, UV/VIS, and resonance Raman spectroscopy. To interpret the experimental results, quantum-chemical calculations were performed. In the case of Sr2+ and Ba2+ ions, the formation of strong sandwich complexes [M(1b)2]2+ of an unusual structure involving stacking interactions was established; the dye molecules are arranged one above another in the complex according to the head-to-head' pattern.
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| 12. |
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| 13. |
- Grönros, Julia, 1978, et al.
(författare)
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Effects of rosuvastatin on cardiovascular morphology and function in an ApoE-knockout mouse model of atherosclerosis
- 2008
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Ingår i: American Journal of Physiology-Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 295:5
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of rosuvastatin on plaque progression and in vivo coronary artery function in apolipoprotein E-knockout (ApoE-KO) mice, using noninvasive high-resolution ultrasound techniques. Eight-week-old male ApoE-KO mice ( n = 20) were fed a high-fat diet with or without rosuvastatin (10 μmol·kg−1·day−1) for 16 wk. When compared with control, rosuvastatin reduced total cholesterol levels ( P < 0.05) and caused significant retardation of lesion progression in the brachiocephalic artery, as visualized in vivo using an ultrasound biomicroscope ( P < 0.05). Histological analysis confirmed the reduction of brachiocephalic atherosclerosis and also revealed an increase in collagen content in the statin-treated group ( P < 0.05). Coronary volumetric flow was measured by simultaneous recording of Doppler velocity signals and left coronary artery morphology before and during adenosine infusion. The hyperemic flow in response to adenosine was significantly greater in left coronary artery following 16 wk of rosuvastatin treatment ( P < 0.001), whereas the baseline flow was similar in both groups. In conclusion, rosuvastatin reduced brachiocephalic artery atherosclerotic plaques in ApoE-KO mice. Coronary artery function assessed using recently developed in vivo ultrasound-based protocols, also improved.
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| 14. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 15. |
- Lee, S. D., et al.
(författare)
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
- 2019
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:11
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Tidskriftsartikel (refereegranskat)abstract
- Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of dietinduced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specific knockout mice revealed that IDOL affects energy balance, not through its actions in peripheral metabolic tissues (liver, adipose tissue, endothelium, intestine, and skeletal muscle) but by controlling lipoprotein receptor abundance in neurons. Single-cell RNA sequencing of the hypothalamus demonstrated that IDOL deletion altered gene expression linked to the control of metabolism. Finally, we identified very low-density lipoprotein receptor (VLDLR) rather than low-density lipoprotein receptor (LDLR) as the primary mediator of the effects of IDOL on energy balance. These data identify a role for the neuronal IDOL-VLDLR pathway in metabolic homoeostasis and diet-induced obesity.
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| 16. |
- Odak, I., et al.
(författare)
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Teachers’ Social and Emotional Competencies : A Lever for Social and Emotional Learning in Schools
- 2023
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Ingår i: Sociologija i Prostor. - : Institute for Social Research Zagreb. - 1846-5226. ; 61:1, s. 105-122
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Tidskriftsartikel (refereegranskat)abstract
- The present paper focuses on social and emotional learning, and highlights empirical findings on its importance for teachers, students and schools. The importance of social and emotional learning in school settings has been a central focus of research for the last 30 years. The development of teachers’ social and emotional competencies has been an essential factor for improving social and emotional learning of students. Only when teachers are able to create a school climate in which students feel included and welcome, students can develop and enhance their social and emotional competencies. In this paper, we outline the main conceptual frameworks on social and emotional learning, emphasizing the CASEL framework, relevant for both young people and adults. We proceed by focusing on teachers’ social and emotional competencies, as teachers are one of the key figures for fostering and developing social and emotional competencies in school settings. Afterwards, we address the issue of development of teachers’ social and emotional competencies in various settings. The last part of the paper links teachers’ and students’ social and emotional competencies. We stress the importance of teachers’ social and emotional competencies for healthy teacher-student relationships, and students’ well-being and academic achievement. As teachers also need support for the development of these competencies, we advocate for comprehensive school-wide approach, in order to ensure the successful implementation of social and emotional learning in classrooms.
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| 17. |
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| 18. |
- Ozgumus, T., et al.
(författare)
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Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
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| 19. |
- Taskinen, M. R., et al.
(författare)
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Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282, s. 187-201
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Association for the Publication of the Journal of Internal Medicine Background: Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. Objectives: To assess the effects of fructose (75 g day −1 ), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. Methods: We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Results: Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Conclusion: Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.
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| 20. |
- Tattikota, Sudhir G., et al.
(författare)
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miR-184 Regulates Pancreatic beta-Cell Function According to Glucose Metabolism
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:33, s. 20284-20294
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Tidskriftsartikel (refereegranskat)abstract
- In response to fasting or hyperglycemia, the pancreatic beta-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the beta-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the beta-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.
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| 21. |
- Vergari, Elisa, et al.
(författare)
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Somatostatin secretion by Na+-dependent Ca2+-induced Ca2+ release in pancreatic delta-cells.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islets are complex micro-organs consisting of at least three different cell types: glucagon-secreting α-, insulin-producing β- and somatostatin-releasing δ-cells1. Somatostatin is a powerful paracrine inhibitor of insulin and glucagon secretion2. In diabetes, increased somatostatinergic signalling leads to defective counter-regulatory glucagon secretion3. This increases the risk of severe hypoglycaemia, a dangerous complication of insulin therapy4. The regulation of somatostatin secretion involves both intrinsic and paracrine mechanisms5 but their relative contributions and whether they interact remains unclear. Here we show that dapagliflozin-sensitive glucose- and insulin-dependent sodium uptake stimulates somatostatin secretion by elevating the cytoplasmic Na+ concentration ([Na+]i) and promoting intracellular Ca2+-induced Ca2+ release (CICR). This mechanism also becomes activated when [Na+]i is elevated following the inhibition of the plasmalemmal Na+-K+ pump by reductions of the extracellular K+ concentration emulating those produced by exogenous insulin in vivo6. Islets from some donors with type-2 diabetes hypersecrete somatostatin, leading to suppression of glucagon secretion that can be alleviated by a somatostatin receptor antagonist. Our data highlight the role of Na+ as an intracellular second messenger, illustrate the significance of the intraislet paracrine network and provide a mechanistic framework for pharmacological correction of the hormone secretion defects associated with diabetes that selectively target the δ-cells.
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| 22. |
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| 23. |
- Abdellaoui, G., et al.
(författare)
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Science and mission status of EUSO-SPB2
- 2022
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Ingår i: 37th International Cosmic Ray Conference, ICRC 2021. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- The Extreme Universe Space Observatory on a Super Pressure Balloon II (EUSO-SPB2) is a second generation stratospheric balloon instrument for the detection of Ultra High Energy Cosmic Rays (UHECRs, E > 1 EeV) via the fluorescence technique and of Very High Energy (VHE, E > 10 PeV) neutrinos via Cherenkov emission. EUSO-SPB2 is a pathfinder mission for instruments like the proposed Probe Of Extreme Multi-Messenger Astrophysics (POEMMA). The purpose of such a space-based observatory is to measure UHECRs and UHE neutrinos with high statistics and uniform exposure. EUSO-SPB2 is designed with two Schmidt telescopes, each optimized for their respective observational goals. The Fluorescence Telescope looks at the nadir to measure the fluorescence emission from UHECR-induced extensive air shower (EAS), while the Cherenkov Telescope is optimized for fast signals (∼10 ns) and points near the Earth's limb. This allows for the measurement of Cherenkov light from EAS caused by Earth skimming VHE neutrinos if pointed slightly below the limb or from UHECRs if observing slightly above. The expected launch date of EUSO-SPB2 is Spring 2023 from Wanaka, NZ with target duration of up to 100 days. Such a flight would provide thousands of VHECR Cherenkov signals in addition to tens of UHECR fluorescence tracks. Neither of these kinds of events have been observed from either orbital or suborbital altitudes before, making EUSO-SPB2 crucial to move forward towards a space-based instrument. It will also enhance the understanding of potential background signals for both detection techniques. This contribution will provide a short overview of the detector and the current status of the mission as well as its scientific goals.
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| 24. |
- Adamonyte, G, et al.
(författare)
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Morphological variation and taxonomic characters in Cribraria (Myxomycetes) from the Great Smoky Mountains National Park in eastern USA
- 2010
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Ingår i: NOVA HEDWIGIA. - : Schweizerbart. - 0029-5035. ; 90:3-4, s. 303-320
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Tidskriftsartikel (refereegranskat)abstract
- Cribraria is one of the most taxonomically difficult genera in the myxomycetes. The genus as a whole is well characterized but several of the currently accepted species are vaguely defined with ranges of morphological variation overlapping. Morphological characters are discussed based on specimens of eleven species from the Great Smoky Mountains National Park in eastern U.S.A. Cribraria persoonii, C. piriformis and C. vulgaris are reported from the National Park for the first time, making a total of 21 species of the genus so far recorded in the Park. Other species discussed in some detail include C. elegans, C. intricata. C. languescens, C. macrocarpa and C. oregano. Light photomicrographs illustrate most of the species.
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| 25. |
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| 26. |
- Alssema, M, et al.
(författare)
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The evaluation of screening and early detection strategies for type 2 diabetes and impaired glucose tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes
- 2011
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 54:5, s. 1004-1012
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors. METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques. RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity. CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.
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| 27. |
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| 28. |
- Andersson, Fredrik N G, et al.
(författare)
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Det finanspolitiska ramverket efter coronapandemin
- 2021
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Ingår i: I en tid av pandemi – en ESO-antologi med samhällsvetenskapliga reflektioner. - 9789152500699 ; , s. 151-176
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna rapport är att diskutera om Sverige bör överge det nuvarande ramverkets regler och följa med i den internationella trenden med kraftigt ökad offentlig skuldsättning. Vårt svar är nej. Argumenten för att överge det nuvarande ramverket är svaga. Vi får inte glömma att ramverket bidragit till årtionden av ekonomisk stabilitet i Sverige – inte minst nu under coronakrisen. Eventuella reformer av ramverket bör istället förstärka snarare än försvaga det.
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| 29. |
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| 30. |
- Armour, Sarah L., et al.
(författare)
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Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells
- 2023
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Ingår i: DIABETES. - 0012-1797 .- 1939-327X. ; 72:10, s. 1446-1459
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Tidskriftsartikel (refereegranskat)abstract
- Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from alpha-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic alpha-cells remain unclear. Here we show that in alpha-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the alpha-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion.Article Highlights It has become clear that dysregulation of glucagon secretion and alpha-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in alpha-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.
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| 31. |
- Athab Abduljabbar, Zahra, et al.
(författare)
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Chewing side preference and laterality in patients treated with unilateral posterior implant-supported fixed partial prostheses
- 2022
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Ingår i: Journal of Oral Rehabilitation. - : Wiley. - 0305-182X .- 1365-2842. ; 49:11, s. 1080-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not clear to what extent chewing is improved by unilateral oral rehabilitation with implant-supported fixed partial prostheses (ISFPPs). Objectives: This study aimed to investigate whether patients treated with unilateral ISFPPs in the maxilla use their prostheses during mastication to the same extent as they used their contralateral natural teeth. A further aim was to investigate whether there is a correlation between preferred chewing side and laterality. Methods: Chewing side preference was assessed in 15 participants treated with unilateral ISFPPs in the maxilla. The first, second, third, fifth and tenth chewing cycles were assessed, and the test was repeated 10 times. All participants also answered a questionnaire about their chewing side preference. Results: Most of the participants presented bilateral chewing, but two (13%) chewed only on the ISFPP. There was no statistically significant association between the objectively assessed chewing side and dental status (natural teeth or ISFPPs) during any of the recorded chewing cycles (p >.1). There were statistically significant correlations between both the subjectively reported usually preferred chewing side and the subjective chewing side preference during the test and the objectively assessed chewing side for the first three chewing cycles (p <.01). No correlation was found between handedness and the objectively assessed chewing side. Conclusion: In the present study, most participants chewed bilaterally, and chewing was performed both on the ISFPP and on the natural teeth. No correlation was found between the preferred chewing side, objectively or subjectively determined and laterality.
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| 32. |
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| 33. |
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| 34. |
- Bastholm Rahmner, Pia, et al.
(författare)
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Physicians perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system
- 2004
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Ingår i: International journal of health care quality assurance incorporating leadership in helath services. - : Emerald. - 1366-0756 .- 2051-3135. ; 17:4, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- Seeks to identify physicians' perceptions of possibilities and obstacles prior to implementing a computerised drug prescribing support system. Details a descriptive, qualitative study, with semi-structured individual interviews of 21 physicians in the Accident and Emergency Department of South Stockholm General Hospital. Identifies four descriptive categories for possibilities and obstacles. Concludes that gaining access to patient drug history enables physicians to carry out work in a professional way – a need the computerised prescription support system was not developed for and thus cannot fulfil. Alerts and producer-independent drug information are valuable in reducing workload. However, technical prerequisites form the base for a successful implementation. Time must be given to adapt to new ways of working.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Berkelmans, G. F. N., et al.
(författare)
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Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 145, s. 70-80
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting.& nbsp;Study design and setting: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ? diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naive approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.& nbsp;Results: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).& nbsp;Conclusion: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing. (C)& nbsp;2022 Elsevier Inc. All rights reserved.
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| 41. |
- Bicaku, Ani, 1988-, et al.
(författare)
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Interacting with the arrowhead local cloud : On-boarding procedure
- 2018
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Konferensbidrag (refereegranskat)abstract
- Industrial automation systems are advancing rapidly and a wide range of standards, communication protocols and platforms supporting the integration of devices are introduced. It is therefore necessary to design and build appropriate tools and frameworks that allow the integration of devices with multiple systems and services. In this work we present the Arrow-head Framework, used to enable collaborative IoT automation and introduce two support core systems, SystemRegistry and DeviceRegistry, which are needed to create a chain of trust from a hardware device to a software system and its associated services. Furthermore, we propose an on-boarding procedure of a new device interacting with the Arrowhead local cloud. This ensures that only valid and authorized devices can host software systems within an Arrowhead local cloud.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Carlsson, Lena, et al.
(författare)
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Association of cystatin C with prostasomes in human seminal plasma
- 2011
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Ingår i: International Journal of Andrology. - : Wiley. - 0105-6263 .- 1365-2605. ; 33:4, s. 363-368
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Tidskriftsartikel (refereegranskat)abstract
- It was recently elucidated that cystatin C, a protein targeted to the classical secretory pathway by its signal peptide sequence, can also be secreted in association with exosomes. Accordingly, we wanted to investigate whether there is a secretory link between cystatin C and prostasomes in human seminal plasma. Cystatin C concentrations in seminal plasma from 50 men including 6 vasectomized men were measured by turbidimetry on an Architect Ci8200. Some of the seminal plasma samples were also analysed utilizing an Epics Profile XL-MCL cytometer. We found high concentrations of cystatin C in seminal plasma. The 2.5-97.5 percentiles, performed by bootstrap estimation, were 25.8 [95% confidence interval (CI): 22.3-29.4] to 77.0 mg/L (95% CI: 71.9-82.1). Cystatin C is present in approximately 50 times higher concentration in seminal plasma compared with blood plasma. There was no clear difference as regards seminal plasma content of cystatin C between vasectomized men and the rest of the group. Immunoblot analysis with chicken anti-cystatin C antibody revealed a firm association of cystatin C with prostasomes. Flow cytometric analysis demonstrated that cystatin C was linked to prostasomes also meaning an at least partial prostasomal membrane surface localization.
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| 46. |
- Ceriello, A., et al.
(författare)
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HbA1c variability predicts cardiovascular complications in type 2 diabetes regardless of being at glycemic target
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c target has been relatively unexplored. Methods Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios. Results An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c <= 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c <= 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up. Conclusions These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c.
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| 47. |
- Ceriello, A., et al.
(författare)
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Risk factor variability and cardiovascular risk among patients with diabetes: a nationwide observational study
- 2023
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 30:8, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- Lay Summary The variability of multiple risk factors is associated with an increased risk of cardiovascular events and mortality in patients with Type 2 diabetes. These variabilities interact with one another to identify classes of patients with an increased risk of having an event.Patients with a high variability of both body weight and systolic blood pressure had the greatest risk of cardiovascular diseases or mortality despite a progressive reduction in the mean level of risk factors.Individuals with high weight variability but low systolic blood pressure variability, patients with moderate/high weight variability associated with high HbA1c variability, subjects with moderate/high weight variability and with low/moderate HbA1c variability, as well as those with low weight variability but high total cholesterol variability also showed a significant increase in the risk of an event. Aims Cardiovascular risk factor control fluctuates, tends to change over time, and is potentially impacted by multifactorial interactions. Currently, the presence of risk factors, rather than their variability or interplay with one another, is taken into account to define the population at risk. The association between variability of risk factors and cardiovascular morbidity and mortality risk among patients with Type 2 diabetes mellitus (T2DM) remains debatable. Methods and results Using registry-derived data, we identified 29 471 people with T2DM, without cardiovascular disease (CVD) at baseline, and with at least five measurements of risk factors. Variability for each variable was expressed as quartiles of the standard deviation during 3 years (exposure). The incidence of myocardial infarction, stroke, and all-cause mortality was assessed during 4.80 (2.40-6.70) years following the exposure phase. The association between the measures of variability and the risk of developing the outcome was investigated through multivariable Cox proportional-hazards regression analysis with stepwise variable selection. Then, the recursive partitioning and amalgamation (RECPAM) algorithm was used to explore the interaction among the variability of risk factors associated with the outcome. An association between the variability of HbA1c, body weight, systolic blood pressure, and total cholesterol with the outcome considered was found. Among the six classes of risk identified by RECPAM, patients with a high variability of both body weight and blood pressure had the highest risk [Class 6, hazard ratio (HR) = 1.81; 95% confidence interval (CI) 1.61-2.05] compared with patients with low variability of both body weight and total cholesterol (Class 1, reference), despite a progressive reduction in the mean level of risk factors during successive visits. Individuals with high weight variability but low-moderate systolic blood pressure variability (Class 5, HR = 1.57; 95% CI 1.28-1.68), patients with moderate/high weight variability associated with high/very high HbA1c variability (Class 4, HR = 1.33; 95% CI 1.20-1.49), subjects with moderate/high weight variability and with low/moderate HbA1c variability (Class 3, HR = 1.12; 95% CI 1.00-1.25), as well as those with low weight variability associated with high/very high total cholesterol variability (Class 2, HR = 1.14; 95% CI 1.00-1.30) also showed a significant increase in the risk of an event. Conclusion Combined high variability of two risk factors, particularly body weight and blood pressure, is associated with cardiovascular risk among patients with T2DM. These findings highlight the importance of continuous balancing of multiple risk factors.
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| 48. |
- Ceriello, A., et al.
(författare)
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Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register
- 2021
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes. Methods Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability. Results After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39-1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality). Conclusions High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.
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| 49. |
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| 50. |
- Chriett, S., et al.
(författare)
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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
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